It goes without saying, but it is worth repeating, that rats are not humans and our brains are very different. Nonetheless, a lot of what we learn about the human brain is first learned in rat brains.

With an interesting publication last week in the journal Nature, researchers at Mount Sinai School of Medicine may have embarked on key learning about how biology plays a role in preserving memories. This work was done in rats but may have human implications.

The scientists found that a particular hormone known as IGF-II became more prevalent in a rats brains immediately after learning that entering a dark box resulted in a shock to the foot. They also showed that by injecting the same hormone into rat brains, they could help the rats preserve a memory for a longer period of time.

This finding may prove to clarify our understanding of the biology involved in memory formation and preservation, which could lead to breakthroughs in the field of human memory enhancement. Better insights into the hormones that play a role in the process could also lead one day to supplements that actually improve memory performance.

Again, this is early stage work performed in rats, not in humans. Years of validation work will follow prior to any new "memory pills" that could be based on this insight. It's interesting, but it is early.

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Contributed by: Michael Rafii, M.D., Ph.D - Director of the Memory Disorders Clinic at the University of California, San Diego. ______________________________________

While we sometimes note that the press over-emphasizes the difficulty in diagnosing Alzheimer's disease, there is no doubt that new tests could make the process faster and more accurate. Two recent news stories have converged on this theme.

First, regarding efforts to diagnose Alzheimer's using PET scans to view amyloid plaques in brain, the U.S. Food and Drug Administration’s (FDA) Advisory Committee decided that it could not recommend approval of Amyvid™ (florbetapir) at this time based on the currently available data (13-3); but, voted unanimously (16-0) to recommend approval of Amyvid conditional on specialized training being instituted for the medical professionals who would administer it. It is expected that this training will be formalized, and FDA approval granted by the end of this year.

Second, Kristine Yaffe and colleagues at UCSF published an article in JAMA this week in which they report on a new blood test that predicts subsequent cognitive decline. In the study, they took baseline plasma samples from nearly 1,000 elderly normal volunteers and then followed the participants for nine years, regularly measuring their cognitive performance.

Unlike similar previous studies, Yaffe and colleagues looked at cognitive decline rather than conversion to Alzheimer's disease (AD). They found that a low ratio of two forms of beta-amyloid at baseline correlated with a greater drop in cognition over the duration of the study. Intriguingly, this association was strongest in participants with low levels of education, and much weaker in subjects with more education. This is in accord with the long-standing view that a person’s cognitive reserve can protect against cognitive decline. If the result proves robust in future studies, it may lead to further development of blood tests to monitor for AD.

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This is a question that remains unanswered by current science. However, one could easily be confused by the competing claims in the growing market of "brain training" programs and exercises. Importantly, as we describe in this blog from time to time, conversing and socializing both constitute excellent work-outs for the brain involving multiple realms of cognition.

The online version of the Daily Mail ran a story today that referred to an un-cited research study making this same point. According to the story, researchers in Zurich had performed a review of the published literature on the benefits of brain training and intellectual activities specifically designed to improve cognitive function. They found that, in many studies, subjects who performed the activity under review performed no better than subjects who were instructed to have a conversation.

I remain optimistic that we will identify brief, pleasurable activities that exercise the brain and improve its function. However, to date, the best advice is probably to stay socially and intellectually engaged across a wide range of circumstances and topics.

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Efficacy of treatment for Alzheimer's disease is a topic of frequent debate and disagreement. While the data are relatively clear, the source of the disagreement is often "expectations".

For example, if a person with memory loss and behavioral disturbances due to Alzheimer's disease takes a cholinesterase inhibitor, it would be unrealistic to expect an immediate decline of all symptoms and a full return of cognitive function. Current drugs simply cannot repair damaged brain cells and restore function. More likely, the treatments would mitigate the symptoms and perhaps slow their rate of progression.

So the question is, do these drugs help? If you are expecting them to render a cure, then the answer is "no". But if you are objectively measuring their effect on the quality of the person's life, which incorporates control of symptoms and disease progression, then the answer is "yes".

The National Health Service in the UK has formerly not payed for its citizens with early stage Alzheimer's disease to be treated with cholinesterase inhibitors. That decision may have been based, in part, on unrealistic expectations. However, after collecting several years of additional data and weighing the overall benefits of treatment, they have now reversed that decision.

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The impact of memory on cognitive health is a more or less constant theme in the news.

While many studies have suggested that certain diets, especially those rich with fruits, vegetables, and sources of omega-3 fats (the Mediterranean diet), may be beneficial to the long-term health of the brain, certain evidence of a cause and effect relationship between the two has not been established. However, the evidence continues to move in that direction, including a recent study from Rush Medical College and published in the American Journal of Clinical Nutrition.

In the latest study, nearly 4000 people were tracked at three year intervals since 1993. By using a well validated dietary questionnaire, the researchers showed a significant correlation between adherence to the Mediterranean diet and preserved memory through the later years of their lives.

Add this to the growing list of reasons to take diet seriously as a means of achieving optimal health.

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Last month, a publication in the journal Science suggested a potentially important nuance to our understanding of Alzheimer's pathology.

The most prominent theory in the field, the amyloid hypothesis, posits that excess beta-amyloid in the brain forms plaques which eventually kill brain cells and impair cognition. However, the cause of the excess beta-amyloid is an open question.

The new study, from the University of Washington, suggests that the excess is not due to over-production but by poor clearance of amyloid. The study, on just 24 subjects, twelve of whom had Alzheimer's and twelve of whom were cognitively normal, showed that the subjects with Alzheimer's produced beta-amyloid at about the same rate as the control group but cleared it into the blood stream about 30% slower.

If further validated, this finding could lead researchers down a more well defined path in their efforts to discover new treatments for excess amyloid in the brain.

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This bears repeating: Not every instance of memory loss is a sign of encroaching Alzheimer's disease.

Many common medical conditions, most of them easily and completely treatable, can impair memory. A great review of such conditions is underway online at Behavioral Health Central.

I encourage readers to click the link and read the article but here is a list of the conditions reviewed to date:

Chronic Stress

Depression

Medications

Malfunctioning Thyroid

Pregnancy or Menopause

Excessive Drinking

Head Injury

Normal Aging

I think it is important to point out that a sharp, progressive decline in memory function is not consistent with normal aging. Some aspects of one's recall abilities, such as speed of word and name recall, tend to decline slowly with age, but more serious changes are never normal and should be evaluated by a physician.

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Last week, President Obama signed the National Alzheimer's Prevention Act into law. So what does that mean?

We described the basic spirit of the Act in this earlier post when it passed Congress. It is largely a commitment that we will formulate a strategy and coordinate resources at the federal level. Notably, there were no appropriations (funds) written into the act so, in that regard, there is a risk that the new legislation will be largely symbolic.

Nonetheless, it is a sign of progress toward higher awareness, importance at top levels, and urgency on behalf of the nation. Such a move is a common first step on the path to increased federal funding so I do not despair the current lack of committed funds. This is an important step and, most probably, a step that will catalyze even faster progress in the field.

With so many of the news stories I summarize here, I include caveats about the long and arduous path that basic science must travel before a clinically beneficial advance becomes available to the public. The same caveat applies to the heavy coverage of a new, blood-based diagnostic test recently developed by the Scripps Research Institute and published in the January 7 issue of Cell.

Having said that, this scientific approach strikes me as one worthy of the frothy press it has already spawned.

The approach is exciting in its novelty. Rather than identifying the specific antigens that cause an immune response (production of antibodies) at early stages of a particular disease, and then screening the blood for the presence of those antibodies, the Scripps researchers took another path. They skipped the step at which conventional science is currently focused. That is, they did not bother with the daunting challenge of identifying which specific antigens might stimulate an immune response to fight in early stage Alzheimer's disease.

Rather, in their study, they loaded the blood with thousands of synthetic molecules designed to bind to antibodies of all sorts. By then analyzing the results from patients with Alzheimer's compared to those with Parkinson's and those deemed "healthy", they detected clear evidence that Alzheimer's patients had a much higher concentration of two particular antibodies in their blood. The conclusion, which must be validated with more data, is that these two antibodies are bio-markers for early-stage Alzheimer's disease.

This may prove to be extremely valuable in detecting early stage disease presence, but may pay other dividends as well. If these antibodies do indeed indicate a response to Alzheimer's pathology, then this study may also shed important, new light on the actual disease process which, in turn, could accelerate research on new treatments

Obviously, there is much science to conduct before the world can benefit from this research. But the prospect of leap-frogging one nagging problem in the process, the identification of specific antigens that indicate Alzheimer's, is an exciting proposition.

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Yesterday I attended an advisory meeting for the Alzheimer’s Prevention Initiative. This effort is being orchestrated by academic leaders in the Alzheimer’s field, many of whom have participated in sizable grants from the National Institute of Health in past years. While the particular initiative under discussion is a single project, their clear intention to collaborate with one another, and to plan future research through this coordinated initiative, may have far broader reach. For example, such efforts could greatly bolster efficiency in the application of public research funds in the field.

To be sure, there is more to this initiative than top academics comparing notes prior to planning their grant writing strategies. Also attending the meeting were representatives from the NIH, the FDA, corporate healthcare, and a contingent of international researchers whose collaboration is also being sought. To my knowledge, such alignment and coordination among the constituents of “the healthcare system” is unprecedented.

In my twenty-year career on the commercial side of healthcare, I have never seen the FDA attend a meeting with industry representatives to express their views on how best to get a new drug or device approved. They have always offered clear guidelines and, like the legal system, relied on precedent to apply those guidelines with consistency. But in this meeting, they proactively shared their thinking on how industry should craft an approach.

For instance, a top FDA official shared the agency’s evolving philosophy that, for certain populations at the highest risk of getting Alzheimer’s, they will openly consider approval for treatments with small safety risks, provided that the benefits of treatment outweigh those risks. This is a welcomed stance geared to bringing a near-term solution to a population in need, and I found it to be a remarkably positive and hopeful development.

I was also surprised and encouraged to see fierce industry competitors, perhaps sobered by the collaborative spirit of the meeting, openly discussing strategies for sharing data and thoughts on trial design. All meeting attendees seemed to be caught up in new hopefulness about rapid advance in the field.

The presence of the NIH, with the well-known pressure on their research budgets, suggested they might be most inclined to fund the types of projects that have been carefully vetted by a wide-range of interested parties such as those present at this meeting. This was not lost on the attending researchers, who most likely viewed that as an important incentive to work together toward common goals.

Overall, there were no concrete steps taken or bold commitments made during the daylong discussion and planning session. But there was unmistakable progress toward collaboration and a unified assault on the task of rapidly developing new treatments for Alzheimer’s disease.

I see this as a bright ray of hope for the field and for the population faced with the looming risk of a terrible disease.

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One site I follow for news in this field is the Alzheimer's Research Forum. The postings there can be quite technical as they target medical researchers as an audience. Nonetheless, the content they cover is often the same content as that which gets translated into lay terms (accurately or otherwise) by journalists in the general press.

They recently summarized their opinion of the top research trends in the AD field and I found it to be an excellent summary with a rich set of links to ongoing research stories. From a public impact perspective, I have selected the three from their list that I think are most likely to make a real-world difference, or at least be worthy news stories, in the coming year.

1. Revised Diagnostic Criteria We posted this news followed by our perspective on this change when it was first discussed last summer. I think the new criteria, which define AD based on pathological evidence as opposed to severity of symptoms, provide a great step forward and will enable earlier intervention in a clinical setting.

2. BiomarkersThe ongoing effort to better understand AD pathology brings bio-markers to the forefront of importance. This year will likely see the first FDA approval for an agent that binds to amyloid in the brain and enables visibility on a PET scan. This along with ongoing research on proteins in the blood and spinal fluid, brain volumes, cognitive measures, and a host of other bio-markers portends a year of advance for the field.

3. The Amyloid Hypothesis (or hypotheses)As described by the editors at Alzheimer's Forum, last year saw advances in understanding of amyloid's "...production, aggregation, function, and toxicity". All of this new knowledge must be assimilated into the evolving hypotheses about the role of beta-amyloid in Alzheimer's disease.

While there is much work underway in this field and many facets to the complex problems caused by Alzheimer's disease, the three noted trends above will certainly be central themes in the news during the coming year. Follow along with our posts at this blog to stay abreast of all developments and to understand the likely effects of each.

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It is that season when it is enjoyable, and in some ways instructive, to pause and reflect on the passing of another year.It is also an excellent time for setting priorities and establishing habits that we will be happy to reflect upon twelve months from now.With that in mind, this article suggests 5 simple practices with clear “brain health” benefits that you may wish to consider as you embark on a fresh new year.

To be sure, there are higher ideals than those I have listed here, toward which we could all strive.However, my intention is to provide readers with some ideas that are relatively easy to pursue but can still yield important benefits; the goal is to offer maximal return for minimal effort and sacrifice.

With that said, here are five considerations for starting fresh in 2011:

1. Improve Cardio-Vascular Health

This suggestion is not new but deserves repeating because it has been proven beyond a doubt that good cardio-vascular health leads to better over all health and lower risks for heart disease, diabetes, and Alzheimer’s disease.What is new is certain evidence about how easy it may be to start moving the needle in the right direction.

Improving cardio fitness need not involve strenuous exercise and really doesn’t even require that you sweat.Walking is one of the overall best and most underrated forms of exercise and can often be incorporated into daily errands.Also, don’t think that because walking is easier than running or swimming that you must do it longer to gain a benefit; a daily 30-minute walk is immensely beneficial to a person with no current routine of physical exercise.Especially if the walk can be augmented with a few trips up and down the stairs in lieu of the usual elevator ride.

In terms of staying motivated to maintain a routine of physical exercise, try to find a quantitative measure that will reveal your progress and keep you looking for more gains.In the past, much emphasis has been placed on body weight, a measure that is easy to obtain but can be difficult to improve.As an alternative, check your pulse rate at the end of your work out and track it for one month of daily walks; you might be surprised to see it fall.When you consider how many beats of your heart you can save over the course of a year by keeping your heart rate low, it can be very motivating.

Also, whether or not you suffer from high blood pressure or high cholesterol, be sure to get these measures from your physician during your next check-up and keep track of them as you exercise.Even something as simple as a daily walk is good for your brain and can produce meaningful improvements in both of these bio-markers as you gain better fitness.

2. Reduce Stress

This suggestion might top the all time list of things that are easy to suggest but difficult to achieve.However, it turns out that for many of us, a high percentage of the daily stresses we encounter are self-inflicted.That’s right; choices we make and attitudes we willingly assume end up creating stress that we could otherwise avoid.

Reducing stress is important because we know how detrimental stress can be to our health.Real physical processes are triggered by emotional reactions to stress and, as far as our science can tell, none of those processes are beneficial while all have harmful side effects.

Here is a simple suggestion for reducing stress that, although it won’t work for all of you, must be tried by the rest of you before you can fully believe its effects.Put simply, you should make a conscious decision to drive with patience and courtesy.Look for other drivers trying to cut traffic and motion them in.Don’t speed up to close the gap when another car wishes to enter your lane; slow down and allow them in.Embrace yellow lights for the opportunity they foretell to pause for a moment – this is certainly less stressful than treating them as a threat to your rapid progress.Don’t tailgate or change lanes incessantly seeking opportunities to move one car length closer to the front of the crawling traffic; it is just not worth it.Instead, accept the pace, listen to some music, and keep an eye out for other drivers who might benefit from your courteous cooperation.

If you are not aggressive driver and cannot benefit from that tip, perhaps you can benefit from becoming a less aggressive “parker”.When visiting an establishment with a large parking lot, rather than seeking the spot nearest to the entrance, subjecting yourself to the anxiety of passing up a mediocre spot for the possibility of finding a better one, all the while monitoring the flow of motorists who might be competing for the best spot, try driving to the far end of the lot and parking in the open expanse of remote spots.It is a stress-free approach with the added benefit of a short cardio workout as you walk to your final destination.

While this might seem silly, it’s a step toward avoiding self-inflicted stress that just might carry over into other realms of your life as well.Get the right attitude, reduce your stress, and enjoy a healthier brain and body.

3. Stay Socially Active

While most of us are not in danger of becoming accidental hermits, making new friends and interacting socially are activities that have been documented to decline as we age.We are most prolifically social as young students, followed by fairly intense socialization in adulthood when our children are students, and we tend to be least active when we are older and our children have grown and moved on.

Much research on the benefits of intellectual stimulation, the act of using our brains in challenging ways, has shown a positive correlation with maintained cognitive health.I will write more on that below but will make a separate point here.Meeting people, learning about them, interacting and cooperating with groups, and cultivating relationships are all activities that require deep and comprehensive cognitive activity.In socializing, especially with persons we are still getting to know, we use memory, verbal skills, and judgment along with a poorly understood melding of emotions and executive function.In the opinion of many scientists, socializing may be the best mental activity we have.

Two great ideas for remaining socially active are club membership and volunteering.While you may or may not have interests that lend themselves easily to club membership, a regular card game or social activity with a committed group brings the same benefits.As for volunteering, hospitals, churches, and many non-profit organizations are begging for help in nearly every community.Incidentally, one of the most meaningful gifts you can offer through volunteering is friendship and interaction with a lonely, usually elder, person.Doing so will yield a double benefit because every interaction will be a work-out for both of your brains, not to mention the good it will do for your hearts.

4. Eat Well

You had to know this one was coming.As I did with the section on cardio-vascular fitness, I will try to present this in a new perspective that might be easier to embrace than those perspectives you have heard in the past.

Here is my fresh take on eating well.You needn’t necessarily deny yourself the junk food you’ve grown to love nor worry too much about your daily intake of calories.You do need, however, to worry about getting proper nutrition first.While consuming empty calories is harmful because it leads to weight gain and poor vascular health, the more damaging impact is that it strips away your appetite and prevents consumption of necessary vitamins and nutrients.A fresh approach to diet in the new year might be to focus first on what you should eat and set, as a second goal, the elimination of foods that you should not.

The good news is that the diet shown to produce the best vascular health was also shown this year to also promote the best cognitive health.One should be sure to consume a diet rich in cruciferous and green leafy vegetables, nuts, fish, and tomatoes and low in red meat and high-fat dairy products.Ideally, you will eventually adopt a diet whereby you take in what you need and avoid what you do not, but an easy place to start is to ensure that you get enough fruits and vegetables prior to filling up on junk; this will offer the best opportunity to keep your brain functioning at a high level in the new year.

5. Seek Intellectual Stimulation

If you have pondered the health of your brain at all, you have likely read or heard about the importance of ongoing intellectual stimulation.While it is not yet completely understood, it does appear that active brains decline more slowly with age than those that are relatively unchallenged.

A potential red herring in the discussion is the value of crossword puzzles, sudoku, and the like.Yes, they are mentally challenging activities but they may not produce the rich neural rewards that other activities, such as socializing, might yield.The key seems to be related to the concept of “learning”.If you don’t know the rules of crossword or sudoku then these may be great activities for your brain.However, if you know how the games are played, then merely working through new forms of each puzzle requires no new learning and may offer few benefits to brain health.

Among the most challenging yet rewarding intellectual activities that you pursue are learning to play a musical instrument and learning to speak a foreign language.Both of these have become much easier in the digital age with the advent of tools and software to aid in the learning process.While this might seem counter-intuitive it is actually quite well-grounded.With better tools, the learning becomes easier so the process yields faster proficiency and remains interesting through time.Despite the ease, the learning is real and the brain builds new circuits in accordance with the new learning.The whole process can be great fun, deeply rewarding, and very good for your brain.

So there you have 5 good suggestions to start fresh in the new year and keep your brain healthy in the process.Work on that cardio-vascular fitness, reduce your stress, stay socially active, eat well, and challenge your brain with new learning.If you do so, you can expect that twelve months from now you can look back with clarity and reflect on a year when you made a worthy commitment to the health of your brain.

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